Phase 1b Safety Study of Xevinapant, Weekly Cisplatin, and RT in Participants With Unresected LA SCCHN (HyperlynX)

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06056310

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

Enrollment

Locations

Arm

18.5

Anticipated Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the tolerability and safety of Xevinapant when added to weekly cisplatin-based concurrent chemoradiotherapy (CRT) in the treatment of participants with unresectable locally advanced squamous cell carcinoma of the head and neck, suitable for definitive chemoradiotherapy.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: Xevinapant Drug: Cisplatin Radiation: intensity-modulated radiation therapy (IMRT)	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Single Arm, Open Label, Phase 1b Study of Xevinapant in Combination With Weekly Cisplatin and Intensity-modulated Radiotherapy to Assess Safety and Tolerability in Participants With LA SCCHN, Suitable for Definitive Chemoradiotherapy (HyperlynX)

Anticipated Study Start Date :

Oct 2, 2023

Anticipated Primary Completion Date :

Apr 1, 2025

Anticipated Study Completion Date :

Apr 16, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Xevinapant + Cisplatin + IMRT Participants will receive first 3 cycles of xevinapant once daily in combination therapy with weekly cisplatin and radiotherapy and 3 cycle of monotherapy of xevinapant from Day 1 to Day 14, per 3-week cycle (Each cycle is of 3 weeks).	Drug: Xevinapant Participants will receive first 3 cycles of xevinapant once daily in combination therapy with weekly cisplatin and radiotherapy and 3 cycle of monotherapy of xevinapant from Day 1 to Day 14, per 3-week cycle (Each cycle is of 3 weeks). Other Names: Debio 1143 Drug: Cisplatin Participants will receive weekly cisplatin for 7 weeks on Cycle 1 Day 2 (C1D2), C1D9, C1D16, C2D2, C2D9, C2D16, and C3D2). Radiation: intensity-modulated radiation therapy (IMRT) Participants will receive 70 Gray (Gy) of IMRT in 35 fractions, 2 Gy/fraction, 5 days/week

Arm

Intervention/Treatment

Experimental: Xevinapant + Cisplatin + IMRT

Participants will receive first 3 cycles of xevinapant once daily in combination therapy with weekly cisplatin and radiotherapy and 3 cycle of monotherapy of xevinapant from Day 1 to Day 14, per 3-week cycle (Each cycle is of 3 weeks).

Drug: Xevinapant

Other Names:

Debio 1143

Drug: Cisplatin

Participants will receive weekly cisplatin for 7 weeks on Cycle 1 Day 2 (C1D2), C1D9, C1D16, C2D2, C2D9, C2D16, and C3D2).

Radiation: intensity-modulated radiation therapy (IMRT)

Participants will receive 70 Gray (Gy) of IMRT in 35 fractions, 2 Gy/fraction, 5 days/week

Outcome Measures

Primary Outcome Measures

Number of Participants with Dose limiting toxicity (DLT)-like events [From Day 1 up to 5 Weeks]

Secondary Outcome Measures

Number of Participants with Adverse Events (AEs) and Treatment-Related AEs (TRAE) [From Day 1 up to 18 weeks (Each cycle is of 3 Weeks)]
Absolute changes in estimated glomerular filtration rate (eGFR) [From Screening up to Cycle 3 Day 4 (Day 67)]
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 criteria as assessed by Investigator [Time from first administration of study intervention until Progressive Disease (PD) or death, whichever is earlier assessed approximately up to 1.6 years]
Progression Free Survival (PFS) According to RECIST version 1.1 Criteria as Assessed by Investigator [Time from first administration of study intervention until PD or death, whichever is earlier assessed approximately up to 1.6 years]
Locoregional Control (LRC) According to RECIST version 1.1 Criteria As assessed by Investigator [From randomization to the earliest between PFS event (progression at the site of the primary tumor or the locoregional lymph nodes) or End of Study assessed approximately up to 1.6 years]
LRC is defined as the time from date of the first treatment until date of the first occurrence of progression at the site of the primary tumor or the locoregional lymph nodes.
Time to Subsequent Systemic Cancer Treatments [From randomization to the earliest between PFS event (progression at the site of the primary tumor or the locoregional lymph nodes) or End of Study, assessed approximately up to 1.6 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants having an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 - 1
Histologically confirmed diagnosis in previously untreated Locally Advanced Squamous Cell Carcinoma of Head and neck (LA SCCHN) patient (Stage III, IVA, or IVB according to the American Joint Committee on Cancer [AJCC]/ Tumor Nodes and metastases (TNM) Staging System, 8th Edition) suitable for definitive Chemoradiotherapy (CRT), with one of the following primary sites: oropharynx (OPC) Human Papillomavirus (HPV)-negative, hypopharynx, and larynx
Participant should be able to swallow liquids or has an adequately functioning feeding tube, gastrostomy, or jejunostomy in place. For participants requiring liquid nutrition at baseline or during the study including the follow-up period, access to liquid nutrition supply should be ensured
Participant with evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by CT scan and/or MRI, based on RECIST v 1.1.
Adequate hematological, hepatic, and renal function as defined in the protocol
Other protocol defined inclusion criteria could apply

Exclusion Criteria:

Primary tumor of nasopharyngeal, paranasal sinuses, nasal, or oral cavity, salivary, thyroid, or parathyroid gland pathologies, skin, or unknown primary site
Metastatic disease (Stage IVC as per AJCC/TNM, 8th Edition)
Existing need of a hearing aid or greater than or equal to (>=) 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated
Known history of infection with human immunodeficiency virus (HIV). If unknown history of HIV, an HIV screening test is to be performed and participants with positive serology for HIV-1/2 must be excluded
Known gastrointestinal disorder with clinically established malabsorption syndrome and major gastrointestinal surgery in the last 12 months that may limit oral absorption
Other protocol defined exclusion criteria could apply